The FDA is investigating reports of Covid-19 relapse after taking Pfizer Antiviral
The FDA is investigating reports of Covid-19 relapse after taking Pfizer Antiviral

The FDA is investigating reports of Covid-19 relapse after taking Pfizer Antiviral

Having a rebound of Covid-19 after taking Paxlovid is not exactly the same as having a rebound relationship. Although both can make you sick in different ways. A post-Paxlovid rebound may occur after you feel better about taking Paxlovid for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Rebound is when, at some point after the five-day course of medication is completed, you experience a relapse of Covid-19 symptoms. And it seems that more and more people have reported such relapses.

For example, there it is pre-printed case report uploaded to The research site on April 26, 2022, by a 71-year-old man who had been fully vaccinated and boosted against Covid-19. He started taking Paxlovid as soon as he tested positive for Covid-19, two days after he had been exposed to the virus. His Covid-19 symptoms virtually disappeared after two days of Paxlovid. Still, his runny nose, sore throat, and difficulty breathing returned, and his SARS-CoV-2 levels rose again nine days after he first tested positive and four days after completing the five-day Paxlovid regimen. . Viral genome sequencing showed that during his initial symptoms and his recurrence of symptoms, he became infected with the BA.1 Omicron subvariant of SARS-CoV-2. Of course, a pre-print is not the same as a peer-reviewed article, and anyone with thumbs, a laptop, and Internet access could, in theory, upload a pre-print. But the authors of the case report (Kalpana Gupta, Judith Strymish, Gary Stack, and Michael Charness) are legitimate physicians from legitimate health systems, VA Connecticut, and Boston Healthcare Systems.

In addition, this has certainly not been the only report of such a recovery. For example, here’s what Tatiana Prowell, MD, an associate professor of oncology at Johns Hopkins School of Medicine tweeted:

And Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor Medical College, tweeted about his case of post-Paxlovid relapse:

As a reminder, Paxlovid received Emergency Use Permit (EUA) back December 22, 2021 from US Food and Drug Administration (FDA) as a treatment for those 12 years and older with mild to moderate Covid-19. These antiviral drugs are supposed to prevent SARS-CoV-2 from making it ugly in your body, which is a non-technical way of saying reproduce in your cells. Although Paxlovid does not put small condoms on the spikes of viruses, it is actually the combination of two different antiviral tablets, nirmatrelvir and ritonavir, packed together. The recommended dose of these antiviral drugs is two 150 mg tablets nirmatrelvir together with a 100 mg tablet ritonavir twice daily for five days, provided you have normal kidney function.

Like Hall & Oates, these two drugs work together. Nirmatrelvir can block the action of an enzyme called MPRO, not to be confused with GoPro. MPRO cleaves two different viral polyproteins, which may not sound very sexy, but are an important step when SARS-CoV-2 wants to reproduce. Meanwhile, ritonavir inhibits cytochrome P450 (CYP) 3A4 enzymes in the liver, which can break down nirmatrelvir and thus leave nirmatrelvir hanging longer in your body.

And like condoms, Paxlovid does not work after reproduction has already taken place. Therefore, it is important to take Paxlovid as soon as you find out that you are positive about Covid-19. If you wait more than five days after the symptoms first appear, the virus can reproduce too much for Paxlovid to make a big difference. So there is a limited window, less than half a Scaramucci, where it will help to take Paxlovid.

Like this NBC News segment shows that the FDA is currently investigating reports of Covid-19 setback cases:

So do these rebound cases mean Paxlovid is not doing its job? No, not necessarily. Just because the symptoms return does not mean that things would not have been even worse without the medication. In addition, it is not yet clear what percentage of people have experienced such relapses. Again stories on Twitter and a pre-print case report are not the same as peer-reviewed studies. While Pfizer’s clinical trials showed possible rebound Covid-19, which occurred in about 2% of those who had received Paxlovid, about 1.5% of those who had only received placebo, also suffered similar relapses. As these two percentages were not statistically significantly different from each other, the conclusion from the clinical trial was that these rebounds were not specific for Paxlovid. Of course, what happens or does not happen in a clinical trial does not necessarily mean that the same will be true in the real world.

So what happens, in the words of Marvin Gaye? One possibility is that the five-day course of the medicine does not turn out to be long enough for everyone. The medicine is supposed to suppress viral replication long enough for your immune system to remove the virus from your body. It’s a bit like smearing deodorant on yourself until you’ve had a chance to take a real shower. Remember that Paxlovid does not remove the virus from your body. It just prevents it from replicating. The amount of time it takes for your immune system to perform this virus clearing task can vary depending on how much virus happens to be in your body and the status of your immune system. It may be that your immune system is not geared enough before the five-day course of the medication is completed. So a question is whether the course of Paxlovid should be longer than five days.

Another possibility is that the Omicron variant may be different enough from previous versions of the virus that the medicine may not be quite as effective. Remember Pfizer’s clinical trials took place last year, while the Delta variant was dominant. So all results can be more Delta-specific.

A third possibility is that the virus has developed resistance to the antiviral drug. While resistance may not be in vain, it may reduce the effectiveness of the medication. Resistance is the reason why antiviral drugs against influenza, such as Tamiflu, may not be as effective against certain influenza strains. And with Covid-19 coronavirus replicating so much, resistance may well develop. Every time SARS-CoV-2 replicates, it can be like a drunk person making photocopies of his or her buttocks. Errors can occur when the virus tries to copy its genetic code, leaving the resulting offspring with mutations and thus different genetic sequences. Some of these mutations may alter viral proteins enough to allow the virus to better avoid the antiviral agent.

Many people who use the antiviral drug may then end up selecting for viruses with such resistance mutations because they are better able to survive. These resistant versions can then eventually become the dominant version of the virus. Therefore, antiviral drugs should not be overused.

Although there was no clear evidence of development of resistance during the clinical trial of Pfizer Paxlovid, the trial may not have lasted long enough to see this possibility. It will be important for public health authorities to track the possible emergence of resistant virus strains and potentially limit the use of Paxlovid if such resistance is found.

A fourth option is re-infection. Could some of the suspected relapses actually be people who become infected and then re-infected in a short time? I covered for Forbes a case where someone has been infected with the Omicron variant within 20 days of being infected with the Delta variant. But it is not clear how common it can be to get two separate infections within such a short period of time.

So if you have a rebound case of Covid-19 after taking Paxlovid, then what should you do? Should you take more of this antiviral medicine? Well, at the moment, things are about as clear as Nutella soup. There is not enough evidence for what to do. And EUA only covers taking the medicine for five days.

Ultimately, more studies, more data and more drug monitoring are needed. All of this is a reminder that while Paxlovid may be a very useful part of dealing with the pandemic, it is not a magic pill. Nothing in life is a magical solution with the exception of avocados or chocolate. Relying solely on a drug to “save you” if you were to get Covid-19 could be like relying on finding a soulmate to save you from your current life. Do not think that the existence of Covid-19 treatments may allow you to forgo other Covid-19 precautions such as face mask and Covid-19 vaccination. Remember Covid-19 interventions are like Swiss cheese, not that you have to start putting them on your ham sandwich. Rather, it means that each precaution or treatment has its specific set of holes. And that with gaps means you should always put at least several Covid-19 precautions on top of each other as long as the pandemic is still going on and the virus is circulating far and wide around you. If you do not maintain other Covid-19 precautions and rely solely on getting Paxlovid when needed, the Covid-19 coronavirus may very well catch you on rebound.

Leave a Reply

Your email address will not be published.